Palisade Bio Announces First Patients Dosed in Phase 1b Study of Oral First-In-Class PDE4 Inhibitor Prodrug, PALI-2108, for the Treatment of Fibrostenotic Crohn’s Disease (FSCD)

Rhea-AI Summary

Palisade Bio (Nasdaq: PALI) announced first patients dosed in its open-label Phase 1b study of PALI-2108, an ileocolonic-targeted PDE4 inhibitor prodrug for fibrostenotic Crohn’s disease (FSCD), on Oct 20, 2025. The study will enroll ~6–12 patients to evaluate safety, tolerability, PK, PD, tissue pharmacology, and molecular responses over a 14-day dosing period. Topline safety, PK, and PD data are anticipated in Q1 2026. Data plus existing UC program results are planned to support a Phase 2 IND submission in H1 2026.

Positive

• Phase 1b dosing initiated (first patients dosed Oct 20, 2025)
• Topline safety/PK/PD data expected Q1 2026
• Phase 2 IND planned H1 2026 using combined FSCD and UC data
• Ileocolonic-targeted prodrug designed for high local exposure

Negative

• Study size limited to ~6–12 patients, reducing statistical power
• 14-day treatment period may limit detection of clinical efficacy
• Primary endpoints focused on PK/PD and tissue signals, not efficacy

Insights

Clinical Development Analyst

First patient dosing in FSCD Phase 1b advances a novel, targeted PDE4 prodrug with near-term data and IND plans.

PALI-2108 has entered an open-label Phase 1b study with approximately 6–12 patients dosed for 14 days to assess safety, tolerability, PK, and PD in fibrostenotic Crohn’s disease. The program intentionally measures tissue pharmacology using paired ileal biopsies, single-nucleus and single-cell RNA sequencing, and PBMC analyses to link drug exposure to molecular changes in inflammatory and fibrotic pathways.

Key dependencies and risks include small cohort size and short dosing duration, which limit clinical signal interpretation and safety breadth. The study focuses on mechanistic readouts and exploratory endoscopic, histologic, and IUS endpoints, so regulatory decisions will rely on follow-up data and confirmatory studies.

Concrete near-term milestones to watch are topline safety, PK, and PD data in Q1 2026 and the planned Phase 2 IND submission in H1 2026. These readouts will determine whether tissue-level pharmacology supports larger efficacy trials.

First dual-acting anti-inflammatory and anti-fibrotic candidate in development for FSCD, a condition with no approved therapies

Topline safety, PK, and PD data anticipated in Q1 2026

Advances ongoing development of PALI-2108 across fibrostenotic Crohn’s disease and ulcerative colitis, with Phase 2 IND submission planned for H1 2026

Carlsbad, CA, Oct. 20, 2025 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”), a clinical-stage biopharmaceutical company developing precision therapies for autoimmune, inflammatory, and fibrotic diseases, today announced that the first patients have been dosed in its Phase 1b clinical study evaluating PALI-2108, a first-in-class, ileocolonic-targeted PDE4 inhibitor prodrug, for the treatment of fibrostenotic Crohn’s disease (FSCD). Topline data are anticipated in the first quarter of 2026.

“The initiation of patient dosing marks a significant milestone in our mission to address fibrostenotic complications in Crohn’s disease, an area with no current approved medical therapies,” said Dr. Mitchell Jones, Chief Medical Officer of Palisade Bio. “This mechanistic study is designed to generate critical insights into how PALI-2108 modulates inflammatory and fibrotic pathways in intestinal tissue. Together with data from our ulcerative colitis studies, these findings will inform our planned Phase 2 development and regulatory interactions in 2026.”

The open-label, exploratory Phase 1b study will enroll approximately 6 to 12 patients with FSCD. The study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of once-daily oral dosing of PALI-2108 over a 14-day treatment period. PALI-2108 is a next-generation phosphodiesterase-4 (PDE4) inhibitor prodrug engineered for targeted activation in the terminal ileum and colon, designed to provide high local tissue exposure with minimal systemic absorption.

In addition to safety and PK/PD assessments, the study will evaluate tissue-level pharmacology and molecular responses using paired ileal biopsies and peripheral blood mononuclear cells (PBMCs). Analyses will include single-nucleus and single-cell RNA sequencing to characterize treatment-induced changes in inflammatory and fibrotic signaling. Exploratory endpoints include endoscopic, histologic, and intestinal ultrasound (IUS) measures to assess structural and inflammatory features of FSCD lesions.

Data from this study, together with results from the Phase 1a/1b ulcerative colitis (UC) program, are expected to support Phase 2 Investigational New Drug (IND) submissions to the U.S. Food and Drug Administration (FDA) in the first half of 2026.

About PALI-2108

PALI-2108 is an orally administered, prodrug engineered for local delivery of phosphodiesterase-4 (PDE4) inhibition to the terminal ileum and colon. The prodrug molecule is gut-restricted and pharmacologically inactive until it reaches the lower intestine, where it is cleaved by bacterial enzymes to release its active PDE4 inhibitor metabolite directly at the site of inflammation and fibrosis. This targeted and slow-release design prevents absorption through the upper gut, achieves sustained local exposure and a longer half-life that enables once-daily dosing, and is engineered to produce a blunted peak plasma concentration to improve the overall therapeutic index. Together, these properties are intended to maximize anti-inflammatory and anti-fibrotic effects while minimizing systemic exposure and reducing class-related tolerability issues, such as nausea and headache, that have limited systemic PDE4 inhibitors.

About Palisade Bio

Palisade Bio is a clinical-stage biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases. The Company believes that by using a targeted approach with its novel therapeutics it will transform the treatment landscape. For more information, please go to www.palisadebio.com.

Forward Looking Statements

Any statements contained in this communication that are not statements of historical fact may be deemed to be forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include but are not limited to: statements regarding the timing and results of clinical trials, the potential therapeutic benefits of PALI-2108, and plans for regulatory submissions. These forward-looking statements are based on the Company’s current expectations. Forward-looking statements involve risks and uncertainties. Important factors that could cause actual results to differ materially from those reflected in the Company’s forward-looking statements include, among others, the timing of enrollment, commencement and completion of the Company’s clinical trials; the Company’s reliance on PALI-2108, and its early stage of clinical development; the risk that prior results, such as signals of safety, activity, dosing or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or clinical trials involving the Company’s product candidates in clinical trials focused on the same or different indications; and other factors that are described in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, filed with the Securities and Exchange Commission (“SEC”) on March 24, 2025, and the Quarterly Reports on Form 10-Q or other SEC filings that are filed thereafter. Investors are cautioned not to put undue reliance on these forward-looking statements. These forward-looking statements speak only as of the date hereof, and the Company expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the Company’s expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

Investor Relations Contact
JTC Team, LLC
Jenene Thomas
908-824-0775
PALI@jtcir.com

Source: Palisade Bio

FAQ

What did Palisade Bio announce about PALI-2108 on Oct 20, 2025 (PALI)?

Palisade announced first patients dosed in a Phase 1b study of PALI-2108 for FSCD and said topline safety, PK, and PD data are expected in Q1 2026.

How many patients will the PALI Phase 1b FSCD study (PALI) enroll and for how long?

The open-label study will enroll approximately 6 to 12 patients with a 14-day once-daily dosing period.

What endpoints will Palisade measure in the PALI-2108 Phase 1b study (PALI)?

The study evaluates safety, tolerability, PK, PD, tissue-level pharmacology, molecular responses, and exploratory endoscopic, histologic, and IUS measures.

When does Palisade plan to file a Phase 2 IND for PALI-2108 (PALI)?

Palisade expects to support a Phase 2 IND submission to the FDA in the first half of 2026 using FSCD and UC program data.

What is the intended advantage of PALI-2108’s ileocolonic targeting (PALI)?

PALI-2108 is engineered for targeted activation in the terminal ileum and colon to provide high local tissue exposure with minimal systemic absorption.